The report by Kupchan and coworkers in 1972 on the bioassay-guided isolation of the potent cytotoxic agent, maytansine from the Ethiopian shrub, Maytenus serrata, raised high hopes for its eventual use as a chemotherapeutic agent for the treatment of cancer. However, clinical trials with maytansine proved disappointing, showing no significant clinical benefits from its administration to human cancer patients. Nevertheless, because of their extremely high potency, maytansine and its congeners continue to command interest.
It is accordingly a primary object of the invention to provide new maytansinoid analogs with improved antitumor activity.